Is CENPF p.Ala285Val (c.854C>T) pathogenic?

CENPF p.Ala285Val (c.854C>T) is classified Likely benign in CENPF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.0962); Ultra-rare (popmax 0.0497%, mid); Associated with Inborn genetic diseases.

What condition is associated with CENPF p.Ala285Val (c.854C>T)?

CENPF p.Ala285Val (c.854C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CENPF p.Ala285Val (c.854C>T) in the general population?

CENPF p.Ala285Val (c.854C>T) is ultra-rare (popmax 0.0497%, mid) (gnomAD).

What do computational predictors say about CENPF p.Ala285Val (c.854C>T)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

CENPF p.Ala285Val

c.854C>T · VCV4611824

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.338	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.57, phastCons 0.91
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.16 · regional, not allelic
Overall
CADD	19.49	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0497% Middle Eastern · 3/6,034 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.0043% 69/1,605,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0497%	2,011
South Asian	0.0067%	14,925
European (non-Finnish)	0.00485%	20,637
Remaining individualsnot grpmax-eligible	0.00322%	31,067
Admixed American	0.0017%	58,806

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CENPF
Protein: p.Ala285Val
Coding: c.854C>T
MANE Select: NM_016343
Type: single nucleotide variant
Location: chr1:214620935 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Residue 285: the 'interaction with snap25 and required for localization to the cytoplasm' region

Full CENPF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CENPF p.Ala285= Benign/Likely benign ★★ same residue
CENPF p.Ala1268Val Uncertain significance ★★ ⚠ same condition
CENPF p.Ala1626Val Uncertain significance ★★ ⚠ same condition
CENPF p.Ala1714Thr Uncertain significance ★★ ⚠ same condition
CENPF p.Ala212Asp Uncertain significance ★★ same condition
CENPF p.Ala2616Val Uncertain significance ★★ ⚠ same condition
CENPF p.Arg1325Lys Uncertain significance ★★ ⚠ same condition
CENPF p.Arg1653Trp Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cenpf-p-ala285val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown